Modulation of Heart Rate Variability and Brain Excitability through Acute Whole-Body Vibration: The Role of Frequency.

This cross-over study aimed to explore effects of acute whole-body vibration (WBV) at frequencies of 5-35 Hz on heart rate variability and brain excitability. Thirteen healthy physically active college students randomly completed eight interventions under the following conditions: static upright standing without vibration (CON), static squat exercise (knee flexion 150°) on the vibration platform (SSE), and static squat exercise (knee flexion 150°) combined with WBV at vibration frequency of 5, 9, 13, 20, 25, and 35 Hz. Five bouts × 30 s with a 30-s rest interval were performed for all interventions. The brain's direct current potentials (DCPs), frequency domain variables (FDV) including normalized low frequency power (nLF), normalized high frequency power (nHF) and the ratio of LF to HF (LF/HF), along with the mean heart rate (MHR) were collected and calculated before and after the WBV intervention. Results suggested that WBV frequency at 5 Hz had a substantial effect on decreasing DCPs [-2.13 µV, t(84) = -3.82, p < 0.05, g = -1.03, large] and nLF [-13%, t(84) = -2.31, p = 0.04, g = -0.62, medium]. By contrast, 20-35 Hz of acute WBV intervention considerably improved DCPs [7.58 µV, t(84) = 4.31, p < 0.05, g = 1.16, large], nLF [17%, t(84) = 2.92, p < 0.05, g = 0.79, large] and the LF/HF [0.51, t(84) = 2.86, p < 0.05, g = 0.77, large]. A strong (r = 0.7, p < 0.01) correlation between DCPs and nLF was found at 5 Hz. In summary, acute WBV at 20-35 Hz principally activated the sympathetic nervous system and increased brain excitability, while 5-Hz WBV activated the parasympathetic nervous system and reduced brain excitability. The frequency spectrum of WBV might be manipulated according to the intervention target on heart rate variability and brain excitability.

Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Comparing the Oxford Digital Multiple Errands Test (OxMET) to a real-life version: Convergence, feasibility, and acceptability.

We aimed to assess the convergence, feasibility, and acceptability of the Oxford Digital Multiple Errands Test (OxMET) and the in-person Multiple Errands Test-Home version (MET-Home). Participants completed OxMET, MET-Home, Montreal Cognitive Assessment (MoCA), and questionnaires on activities of daily living, depression, technology usage, mobility, and disability. Forty-eight stroke survivors (mean age 69.61, 41.67% female, and average 16.5 months post-stroke) and 50 controls (mean age 71.46, 56.00% female) took part. No performance differences were found for healthy and stroke participants for MET-Home, and only found below p = .05 for OxMET but not below the corrected p = .006. Convergent validity was found between MET-Home and OxMET metrics (most r ≥ .30, p < .006). MET-Home accuracy was related to age (B = -.04, p = .03), sex (B = -.98, p = .03), disability (B = -0.63, p = .04), and MoCA (B = .26, p < .001), whereas OxMET accuracy was predicted by MoCA score (B = .40, p < .001). Feedback indicated that the OxMET was easy and fun and more acceptable than the MET-Home. The MET-Home was more stressful and interesting. The MET tasks demonstrated good convergent validity, with the OxMET digital administration providing a more feasible, inclusive, and acceptable assessment, especially to people with mobility restrictions and more severe stroke.

The Puerto Rican Infant Metagenomic and Epidemiologic Study of Respiratory Outcomes (PRIMERO): Design and Baseline Characteristics for a Birth Cohort Study of Early-life Viral Respiratory Illnesses and Airway Dysfunction in Puerto Rican Children.

Epidemiologic studies demonstrate an association between early-life respiratory illnesses (RIs) and the development of childhood asthma. However, it remains uncertain whether these children are predisposed to both conditions or if early-life RIs induce alterations in airway function, immune responses, or other human biology that contribute to the development of asthma. Puerto Rican children experience a disproportionate burden of early-life RIs and asthma, making them an important population for investigating this complex interplay. PRIMERO, the Puerto Rican Infant Metagenomics and Epidemiologic Study of Respiratory Outcomes , recruited pregnant women and their newborns to investigate how the airways develop in early life among infants exposed to different viral RIs, and will thus provide a critical understanding of childhood asthma development. As the first asthma birth cohort in Puerto Rico, PRIMERO will prospectively follow 2,100 term healthy infants. Collected samples include post-term maternal peripheral blood, infant cord blood, the child's peripheral blood at the year two visit, and the child's nasal airway epithelium, collected using minimally invasive nasal swabs, at birth, during RIs over the first two years of life, and at annual healthy visits until age five. Herein, we describe the study's design, population, recruitment strategy, study visits and procedures, and primary outcomes.

Bladder Cancer, Version 3.2024.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

Hidden danger: The long-term effect of ultrafine particles on mortality and its sociodemographic disparities in New York State.

Although previous studies have shown increased health risks of particulate matters, few have evaluated the long-term health impacts of ultrafine particles (UFPs or PM0.1, ≤ 0.1 µm in diameter). This study assessed the association between long-term exposure to UFPs and mortality in New York State (NYS), including total non-accidental and cause-specific mortalities, sociodemographic disparities and seasonal trends. Collecting data from a comprehensive chemical transport model and NYS Vital Records, we used the interquartile range (IQR) and high-level UFPs (≥75 % percentile) as indicators to link with mortalities. Our modified difference-in-difference model controlled for other pollutants, meteorological factors, spatial and temporal confounders. The findings indicate that long-term UFPs exposure significantly increases the risk of non-accidental mortality (RR=1.10, 95 % CI: 1.05, 1.17), cardiovascular mortality (RR=1.11, 95 % CI: 1.05, 1.18) particularly for cerebrovascular (RR=1.21, 95 % CI: 1.10, 1.35) and pulmonary heart diseases (RR=1.33, 95 % CI: 1.13, 1.57), and respiratory mortality (borderline significance, RR=1.09, 95 % CI: 1.00, 1.18). Hispanics (RR=1.13, 95 % CI: 1.00, 1.29) and non-Hispanic Blacks (RR=1.40, 95 % CI: 1.16, 1.68) experienced significantly higher mortality risk after exposure to UFPs, compared to non-Hispanic Whites. Children under five, older adults, non-NYC residents, and winter seasons are more susceptible to UFPs' effects.

Validating the OCS-Plus against a clinical standard: A brief report.

This research aimed to determine the sensitivity and clinical validity of the OCS-Plus, a stroke-specific tablet-based cognitive screening tool, in comparison with the MoCA, a routinely used screening tool, after stroke. Eighty-six patients were recruited from Oxfordshire stroke wards over a 22-month period and completed both screens. Overall, we found that the OCS-Plus has good convergent validity and excellent sensitivity when compared with the MoCA. The OCS-Plus is therefore of potential benefit to those seeking a sensitive screening tool.

Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO GUIDELINE (2017; Amended 2020, 2024).

PURPOSE: Although representing approximately 25% of patients diagnosed with bladder cancer, muscle-invasive bladder cancer (MIBC) carries a significant risk of death that has not significantly changed in decades. Increasingly, clinicians and patients recognize the importance of multidisciplinary collaborative efforts that take into account survival and quality of life concerns. This guideline provides a risk-stratified, clinical framework for the management of muscle-invasive urothelial bladder cancer. METHODOLOGY/METHODS: In 2024, the MIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the previous 2020 amendment. The updated search gathered literature from May 2020 to November 2023. This review identified 3739 abstracts, of which 46 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made regarding neoadjuvant/adjuvant chemotherapy, radical cystectomy, pelvic lymphadenectomy, multi-modal bladder preserving therapy, and future directions. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with MIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Electro-Thermopneumatically Actuated, Adhesion-Force Controllable Octopus-Like Suction Cup Actuator.

A light-weight actuator developed in this work belongs to a class of soft robots, and in a sense, resembles an octopus. Its main function is in the attachment or detachment to a solid surface driven by an electro-thermopneumatic mechanism. In this study, a suction cup similar to that of an octopus is manufactured from an elastomer, which is actuated by an electro-thermopneumatic system, mimicking the movement of the octopus' acetabular muscle. Accordingly, the adhesion force generated by such an actuator is regulated by releasing the inner air or adjusting the cup's elasticity. This actuator is designed to be an assistive device that facilitates the individual's physical strength in case of conditions related to aging or cerebellar disease, or a person who lost limbs. In this study, the actuator capabilities are demonstrated in the form of a grip-assisting glove and prosthetic attacher. Moreover, the adhesion mechanism is quantified by numerical simulations and verified experimentally.

Edge-wise analysis reveals white matter connectivity associated with focal to bilateral tonic-clonic seizures.

OBJECTIVE: Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS. METHODS: T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs in an edge-wise approach to determine specific structural connectivity changes associated with seizure generalization in FBTCS compared to matched FS and HPs. Graph theory metrics were computed on both node- and edge-based connectivity matrices. RESULTS: Edge-wise analyses demonstrated that all significantly abnormal cross-hemispheric connections belonged to the FBTCS group. Abnormal connections associated with FBTCS were mostly housed in the contralateral hemisphere, with graph metric values generally decreased compared to HPs. In FBTCS, the contralateral amygdala showed selective decreases in the structural connection pathways to the contralateral frontal lobe. Abnormal connections in TLE involved the amygdala, with the ipsilateral side showing increases and the contralateral decreases. All the FS findings indicated higher graph metrics for connections involving the ipsilateral amygdala. Data also showed that some FBTCS connectivity effects are moderated by aging, recent seizure frequency, and longer illness duration. SIGNIFICANCE: Data showed that not all STR pathways are equally affected by the seizure propagation of FBTCS. We demonstrated two key biases, one indicating a large role for the amygdala in the propagation of seizures, the other pointing to the prominent role of cross-hemispheric and contralateral hemisphere connections in FBTCS. We demonstrated topographic reorganization in FBTCS, pointing to the specific WM tracts involved.

Modification of Commercial Polymer Coatings for Superhydrophobic Applications.

Superhydrophobic surfaces have been studied extensively over the past 25 years. However, many industries interested in the application of hydrophobic properties are yet to find a suitable solution to their needs. This paper looks at the rapid functionalization of nanoparticles and the fabrication of superhydrophobic surfaces with contact angles > 170°. This was achieved by simply mixing commercial products and applying the new formulation with scalable techniques. First, inexpensive and nontoxic superhydrophobic nanoparticles were made by functionalizing nanoparticles with fatty acids in under an hour. A similar methodology was then used to functionalize a commercial polymer coating to express superhydrophobic properties on it by lowering the coating's surface energy. The coating was then applied to a surface by the spray technique to allow for the formation of hierarchical surface structures. By combining the low surface energy with the necessary roughness, the surface was able to express superhydrophobic properties. Both the particles and the surfaces then underwent characterization and functional testing, which, among other things, allowed for clear differentiation between the functionalization properties of the zinc oxide (ZnO) and the silica (SiO2) nanoparticles. This paper shows that suitable superhydrophobic solutions may be found by simple additions to already optimized commercial products.

Telomerase inhibitors induce mitochondrial oxidation and DNA damage-dependent cell death rescued by Bcl-2/Bcl-xL.

BACKGROUND: Reactivation of telomerase is a hallmark of cancer and the majority of cancers over-express telomerase. Telomerase-dependent telomere length maintenance confers immortality to cancer cells. However, telomere length-independent cell survival functions of telomerase also play a critical role in tumorigenesis. Multiple telomerase inhibitors have been developed as therapeutics and include anti-sense oligonucleotides, telomerase RNA component targeting agents, chemical inhibitors of telomerase, small molecule inhibitors of hTERT, and telomerase vaccine. In general, telomerase inhibitors affect cell proliferation and survival of cells depending on the telomere length reduction, culminating in replicative senescence or cell death by crisis. However, most telomerase inhibitors kill cancer cells prior to significant reduction in telomere length, suggesting telomere length independent role of telomerase in early telomere dysfunction-dependent cell death. METHODS: In this study, we explored the mechanism of cell death induced by three prominent telomerase inhibitors utilizing a series of genetically encoded sensor cells including redox and DNA damage sensor cells. RESULTS: We report that telomerase inhibitors induce early cell cycle inhibition, followed by redox alterations at cytosol and mitochondria. Massive mitochondrial oxidation and DNA damage induce classical cell death involving mitochondrial transmembrane potential loss and mitochondrial permeabilization. Real-time imaging of the progression of mitochondrial oxidation revealed that treated cells undergo a biphasic mitochondrial redox alteration during telomerase inhibition, emphasizing the potential role of telomerase in the redox regulation at mitochondria. Additionally, silencing of hTERT confirmed its predominant role in maintaining mitochondrial redox homeostasis. Interestingly, the study also demonstrated that anti-apoptotic Bcl-2 family proteins still confer protection against cell death induced by telomerase inhibitors. CONCLUSION: The study demonstrates that redox alterations and DNA damage contribute to early cell death by telomerase inhibitors and anti-apoptotic Bcl-2 family proteins confer protection from cell death by their ability to safeguard mitochondria from oxidation damage.

Accuracy of quantitative viral secondary standards: a re-examination.

Interlaboratory agreement of viral load assays depends on the accuracy and uniformity of quantitative calibrators. Previous work demonstrated poor agreement of secondary cytomegalovirus (CMV) standards with nominal values. This study re-evaluated this issue among commercially produced secondary standards for both BK virus (BKV) and CMV, using digital polymerase chain reaction (dPCR) to compare the materials from three different manufacturers. Overall, standards showed an improved agreement compared to prior work, against nominal values in both log10 copies/mL and log10 international unit (IU)/mL, with bias from manufacturer-assigned nominal values of 0.0-0.9 log10 units (either copies or IU)/mL. Standards normalized to IU and those values assigned by dPCR rather than by real-time PCR (qPCR) showed better agreement with nominal values. The latter reinforces prior conclusions regarding the utility of using such methods for quantitative value assignment in reference materials. Quantitative standards have improved over the last several years, and the remaining bias from nominal values might be further reduced by universal implementation of dPCR methods for value assignment, normalized to IU. IMPORTANCE: Interlaboratory agreement of viral load assays depends on accuracy and uniformity of quantitative calibrators. Previous work, published in JCM several years ago, demonstrated poor agreement of secondary cytomegalovirus (CMV) standards with nominal values. This study re-evaluated this issue among commercially produced secondary standards for both BK virus (BKV) and CMV, using digital polymerase chain reaction (dPCR) to compare the materials from three different manufacturers. Overall, standards showed an improved agreement compared to prior work, against nominal values, indicating a substantial improvement in the production of accurate secondary viral standards, while supporting the need for further work in this area and for the broad adaption of international unit (IU) as a reporting standard for quantitative viral load results.